Prognostic value of PD-L1 expression level in metastatic renal cell carcinoma / 中华泌尿外科杂志

Objective:To explore the prognostic value of PD-L1 expression level in patients with metastatic renal cell carcinoma (mRCC).Methods:The clinicopathological and survival data of patients with mRCC in our hospital from Jan 2014 to Apr 2016 were retrospectively analyzed including 46 males and 15 females. The median age of these patients was 56 years(range: 29-75 years), with 41 patients ≤60 years and 20 patients >60 years. The baseline data before the systemic therapy showed 36 patients(59.0%)had 1 metastatic organ and 25 patients (41.0%) had equal or more than 2 organs to be metastasized. Among them, 17 patients(27.9%)had lung metastasis and 54 patients(88.5%)had liver metastasis. Abnormal baseline LDH occurred in 4 patients and 52 patients had normal LDH. Favorite and intermediate risk patients categorized by MSKCC risk stratification accounted for 59.6%(34 patients)and 40.4%(23 patients), respectively. Six patients(9.8%)experienced distant metastasis at initial diagnosis, with 4 of them undergoing primary site resection, and the other 55 patients undergoing radical nephrectomy. PD-L1 expression was detected by the immunohistochemical staining method. PD-L1 staining rate ≥1% detected on the tumor cell membrane was defined as positive expression. The correlation between PD-L1 expression and clinicopathological characteristics were compared. Kaplan-Meier method and log-rank test were used to compare the differences about DFS and OS under different factors. Cox proportional hazards regression model is used for multivariable analysis of survival data.Results:The detailed pathological types of the 61 patients with renal cell carcinoma were classified as 53 clear cell carcinomas, 3 papillary carcinomas, 1 collecting duct carcinoma, 2 translocation renal cell carcinomas and 2 being unclassified. There were 4, 20, 19 and 9 patients categorized as WHO/ISUP nuclear grade 1, 2, 3 and 4, and 26, 12, 20 and 2 patients were categorized as T 1, T 2, T 3 and T 4 stage, respectively. Five patients had regional lymph node metastasis(N+), and the other 56 patients had no regional lymph node metastasis(N-). The numbers of patients categorized as stage Ⅰ, Ⅱ, Ⅲ and Ⅳ diseases according to TNM staging system were 20, 11, 21 and 8, respectively. The total PD-L1 positive rate was 24.6%(15/61). The corresponding PD-L1 expression rate of patients with WHO/ISUP nuclear grade 1-4 were 0(0 patient), 5.0%(1 patient), 31.6%(6 patients)and 44.4%(4 patients), respectively; With the increasing WHO/ISUP nuclear grade, the positive rate of PD-L1 gradually escalated with a linear correlation ( P=0.006). The PD-L1 expression of the normal and abnormal LDH group were 19.2%(10 patients)and 75.0%(3 patients), respectively, with significant difference( P=0.035). Univariate analysis of disease-free survival time(DFS)showed that the prognostic factors include PD-L1( P=0.045), age group( P=0.014), WHO/ISUP nuclear grade( P<0.001), T stage( P=0.015), N stage( P=0.026)and TNM stage( P=0.005). However multivariate analysis only suggested WHO/ISUP nuclear grade as the independent prognostic factors for DFS( HR=1.8, 95% CI 1.1-2.9, P=0.018). Either in univariate or multivariate analysis, PD-L1 was not a prognostic factor for overall survival (OS)of mRCC patients(univariate analysis: P=0.154; multivariate analysis: P=0.902). The independent prognostic factors of OS include WHO/ISUP nuclear grade( HR=3.0, 95% CI 1.1-8.0, P=0.033)and MSKCC risk stratification( HR=5.9, 95% CI 1.2-29.7, P=0.03). Conclusions:This study showed that the higher the WHO/ISUP nuclear grade of patients with mRCC, the higher the positive rate of PD-L1. PD-L1 expression was not the independent prognostic factor for DFS or OS of mRCC.

Clinical characteristics and prognosis of metastatic papillary renal cell carcinoma / 中国肿瘤临床

Objective: To investigate the clinical characteristics, treatment methods, and prognosis of metastatic papillary renal cell car-cinoma (pRCC). Methods: The clinical data of metastatic pRCC patients treated at the Department of Kidney Cancer and Melanoma, Pe-king University Cancer Hospital, were retrospectively analyzed. The prognosis of these patients was stratified through international metastatic renal cell carcinoma database consortium (IMDC) model. Survival and influencing factors were further analyzed using the Kaplan-Meier method and Cox proportional risk regression model. Results: From January 2003 to March 2018, 93 patients (median age, 50.0 years) were diagnosed with metastatic pRCC: 89 (95.7%) typeⅡcases and 4 (4.3%) typeⅠcases. The median follow-up dura-tion was 23.1 months, with 90, 44, and 14 patients having received first-line, second-line, and third-line treatments, respectively. The median overall survival (OS) of the 93 patients was (31.5±5.9) months [95% confidence interval (CI): 19.9-43.1], while the median OS of patients with low-, intermediate-, and high-risk (classified as per the International Metastatic Renal Cell Carcinoma Database Con-sortium [IMDC]) were (100.0±32.8), (38.3±8.2), and (16.4±1.2) months, respectively (high-risk vs. low/intermediate-risk, P<0.001; low-risk vs. intermediate-risk, P=0.015). The median progression free survival (PFS) with first-line treatment was (6.6±0.5) months. And the median PFS of the corresponding three groups stratified by IMDC score were (17.5±5.7), (7.1±2.3), and (5.2±1.5) months, respectively (high-risk vs . low-risk, P=0.002; high-risk vs . intermediate-risk, P=0.01). Conclusions: Metastatic pRCC is noted to have unique biologi-cal characteristics. The IMDC model can be used to predict the efficacy of first-line treatment using tyrosine kinase inhibitors as well as the prognosis of metastatic papillary renal cell carcinoma in such patients.

A pilot study of sunitinib as first-line therapy for metastatic renal cell carcinoma on a 2 weeks on/1 week off intermittent dosing schedule / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the efficacy and safety of sunitinib as first-line therapy for metastatic renal cell carcinoma (mRCC) on a 2 weeks on/1 week off intermittent dosing schedule.</p><p><b>METHODS</b>A total of 11 mRCC patients were enrolled to receive sunitinib 50 mg/day in 2 weeks on/1 week off schedule per 6 weeks till disease progression or intolerable toxicity occurred. The primary end point was progression free survival (PFS), the secondary end points were overall survival (OS), incidence of adverse effects and objective response.</p><p><b>RESULTS</b>The objective response rate in the 11 cases was 45.5% and disease control rate 72.7% (partial response n = 5, stable disease n = 3). Till the last follow up on Dec 2013, the median PFS was 17.0 months (95% CI 7.3 to 26.7 months), and median OS 26.0 months (95% CI 2.2 to 49.8 months). The common adverse events included leucopenia, thrombocytopenia, diarrhea, mucositis and hand-foot skin reaction. Dose reduction to 37.5 mg was seen only in 2 patients without discontinuation.</p><p><b>CONCLUSIONS</b>Sunitinib on an intermittent dosing schedule 2 weeks on /1 week off as first-line therapy for mRCC patients shows a good efficacy and tolerance, with less grade 3-4 drug-related toxicities and a tendency of prolonged PFS in mRCC patients.</p>

Application of Irinotecan in locally advanced or metastatic esophageal carcinoma / 肿瘤研究与临床

Esophageal carcinoma represents high incidence and mortality rate in China.Irinotecan (CPT-11) has shown promising activity in a number of gastrointestinal cancers,including esophageal cancer.This article reviews recent clinical trials of irinotecan-based chemotherapy and radiochemotherapy in esophageal carcinoma.